Molecular analysis suggests oligoclonality and metastasis of endometriosis lesions across anatomically defined subtypes
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Abstract
OBJECTIVE: To investigate the heterogeneity of somatic cancer-driver mutations within patients and across endometriosis types. DESIGN: A single-center cohort, retrospective study. SETTING: Tertiary specialist-care center at a university hospital. PATIENT(S): Patients with surgically and histologically confirmed endometriosis of at least 2 anatomically distinct types (ovarian, deep infiltrating, and superficial). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Specimens were analyzed for the presence or absence of somatic cancer-driver mutations using targeted panel sequencing with orthogonal validation using droplet digital polymerase chain reaction and mutation-surrogate immunohistochemistry. RESULT(S): It was found that 13 of 27 patients had informative somatic driver mutations in endometriosis lesions; of these 13 patients, 9 had identical mutations across distinct lesions. Endometriomas showed a higher mutational complexity, with functionally redundant driver mutations in the same gene and within the same lesions. CONCLUSION(S): Our data are consistent with clonality across endometriosis lesions, regardless of subtype. Further, the finding of redundancy in mutations within the same gene and lesions is consistent with endometriosis representing an oligoclonal disease with dissemination likely to consist of multiple epithelial clones traveling together. This suggests that the current anatomically defined classification of endometriosis does not fully recognize the etiology of the disease. A novel classification should consider genomic and other molecular features to promote personalized endometriosis diagnosis and care.
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Recent molecular analysis studies suggest endometriosis is an oligoclonal disease with dissemination due to multiple epithelial clones traveling together.
“Praetorius et al. have conducted recent molecular analysis studies that suggest endometriosis as an oligoclonal disease with dissemination due to multiple epithelial clones traveling together [ 33 ].”
From Thoracic Endometriosis Syndrome: A Comprehensive Review and Multidisciplinary Approach to Management (2024) · cites this paper as [33]
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- Authors
- Praetorius, T. H., Leonova, A., Lac, V., Senz, J., Tessier-Cloutier, B., Nazeran, T. M., Köbel, M., Grube, M., Kraemer, B., Yong, P. J., Kommoss, S., & Anglesio, M. S.
- Affiliations
- University of British Columbia (CA)
- University of Calgary (CA)
- Universitätsklinikum Tübingen (DE)
- Corresponding author
- Anglesio, Michael S.
- ORCID
- Venue
- Fertility and Sterility
- Publisher
- Elsevier BV
- Published
- 2022-09
- Volume
- 118
- Issue
- 3
- Pages
- 524-534
- ISSN
- 0015-0282 (ISSN-L)
- OpenAlex
- W4282924487
- Cited by
- 43
- References
- 53
- Citations by year
- 2026: 9 · 2025: 14 · 2024: 5 · 2023: 13 · 2022: 1 · 2021: 1
- FWCI
- 6.95
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Fertility and Sterility (publishedVersion, cc-by-nc-nd)
- medRxiv (acceptedVersion, cc-by-nd)
- PubMed (publishedVersion)
- Funders
- Canadian Institutes of Health Research (RS19-609)
- Michael Smith Health Research BC
- BC Cancer Foundation
- Calgary Laboratories Service
- VGH and UBC Hospital Foundation (RS19-621)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Endometriosis Research and Treatment
- Health Sciences › Medicine › Obstetrics and Gynecology › Endometrial and Cervical Cancer Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Keywords
- endometriosis, somatic driver mutations, clonality, oligoclonality, metastasis, endometrioma, deep infiltrating endometriosis, superficial endometriosis
- MeSH terms
- Endometriosis, Endometrium, Female, Humans, Mutation, Neoplasms, Retrospective Studies
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